PhenylketonuriasNCT05174559
Additional Dietary Large Neutral Amino Acids (LNAA) for Improved Symptoms in Adult Classical Phenylktonuria (PKU)
A study testing PreKUnil® LNAA Medical Food for PKU in people with Phenylketonurias, run by University of Southern California at 1 site in United States.
Trial summary
This research investigates the effects of combining a phenylalanine restricted diet (usual care) with LNAA supplementation (adjuvant LNAA) in well-controlled adults with classical PKU. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Phenylketonurias
- What is being tested?
- PreKUnil® LNAA Medical Food for PKU
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2023to 31 Jul 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age ≥ 18 years
- diagnosis of classical PKU (blood phenylalanine ≥1200 µmol pre-treatment or off-treatment
- ≥ 2 PKU-related symptoms with clinically meaningful negative impact on daily life
- is in regular clinical monitoring and is treated with a PKU diet with a natural protein restriction and medical foods
- average blood phenylalanine levels between 360 and 900 µmol in past one year
- able and willing to provide consent
Show all 9Show fewer
- demonstrates capacity to complete all requirements of the protocol
- if on medications approved by the Principal Investigator agrees not to alter dose for duration of study
- has stable daily access to phone, internet, and physical address
Who cannot join
- women who are breastfeeding, pregnant or planning to become pregnant in the next year
- use of adjuvant PKU treatments (LNAAs, Kuvan®, Palinziq®) within past 3 months
- use of psychotropic medications, melatonin, or any serotonin-reuptake inhibitors within past 3 months
- demonstrates insufficient motivation or time required to complete full trial
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Southern California
Los Angeles, California, 90033
About this study
Official title: Can Care of Adult PKU Be Improved With Additional Dietary Large Neutral Amino Acids: An N-of-1 Study
This research investigates the effects of combining a phenylalanine restricted diet (usual care) with LNAA supplementation (adjuvant LNAA) in well-controlled adults with classical PKU. The hypothesis is that symptoms are improved in well-controlled patients who receive adjuvant LNAA therapy compared with diet monotherapy. Six symptomatic classical PKU adults will be enrolled to test the hypothesis in a small series of N-of-1 randomized controlled trials over 18-weeks. All assessments will be collected in patient's homes. A 3-month follow-up period will assess the longer-term effects of adjuvant LNAA in patients who show clinical benefit at the end of the intervention period.
Read the detailed description
Clinical care of PKU confronts an increasing proportion of early-treated well-controlled adults, with a treatment goal that quality of life be as normal as possible. Even adults who have successfully managed their blood phenylalanine levels from birth can have symptoms which impact daily function. New therapies that target symptoms are needed, especially for symptomatic well-controlled classical adults with few treatment options. In Denmark and the LAC+USC U.S. clinic, adults are offered large neutral amino acid (LNAA) supplements when diet monotherapy becomes less effective for symptom management, or the patient wants a less restrictive diet. Many patients report improved symptoms. LNAA supplementation doesn't significantly reduce blood phenylalanine, suggesting a different mechanism for patient perceived benefits. Both LNAA supplementation and a phenylalanine restricted diet aim to improve brain neurotransmitter biochemistry to optimize outcomes through dietary intervention. The overall objective of this research is to evaluate additional dietary LNAAs on symptom management in adults with classical PKU at an individual level. N-of-1 randomized controlled trials will provide the highest level of evidence. The scientific premise is that manipulation of dietary LNAAs affects blood LNAA concentrations. LNAAs compete with phenylalanine for a shared transporter from blood to brain, dependent on blood concentrations and transporter affinities. Higher blood phenylalanine levels in adult PKU, with high transport affinity, produces excessive phenylalanine brain entry at the expense of other LNAAs. Insufficient LNAAs impairs synthesis of chemicals in the brain (neurotransmitters), a suggested mechanism of action for adult PKU symptoms. Additional dietary LNAAs may help to overcome this limitation of adult usual care. The study uses established PKU treatment products (medical foods) and biomarkers, (1) to determine effect of the adjuvant LNAA diet in symptom management; and (2) to evaluate correlations between changes in biomarkers and changes in symptoms during the intervention. Should findings show additive clinical value of LNAAs to the PKU diet, the strategy may become a useful adjunct. For participants, results will bring them closer to evidence-based individualized care. This work could advance the field closer toward personalized management.
- Conditions
- Phenylketonurias
- Being tested
- PreKUnil® LNAA Medical Food for PKU
- Keywords
- N-of-1 randomized controlled trials
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PreKUnil® LNAA Medical Food for PKUOther
PreKUnil® LNAA Medical Food for PKU is a commercially available active LNAA treatment product for PKU. PreKUnil® inactive LNAA is a customized placebo for this research.
| Study group | Role | What they receive |
|---|---|---|
| Active LNAA | Active comparator | Active LNAA tablets are given to each participant in 3 multiple crossovers for a total exposure to the Active Comparator 3 times. The allocation is randomized within each cycle of two treatments (active/inactive). There are 3 total cycles for each participant. The intervention is PreKUnil® tablets. Receives: Other: PreKUnil® LNAA Medical Food for PKU |
| Inactive LNAA | Placebo comparator | Inactive LNAA tablets (placebos) are given to each participant in 3 multiple crossovers for a total exposure to the Inactive Comparator 3 times. The allocation is randomized within each cycle of two treatments (inactive/active). There are 3 total cycles for each participant. The placebo intervention is PreKUnil® placebo tablets. Receives: Other: PreKUnil® LNAA Medical Food for PKU |
What is being measured
The primary outcome is the main question the study is designed to answer.
Personalized Symptom Index
Assesses the subjective effect of the interventions on the personally relevant two most bothersome symptoms for the individual patient as identified in a Symptom Elicitation Interview
Measured: 3 weeks
Secondary outcomes (8)
Absolute plasma phenylalanine concentration, dried blood spots (finger-prick method)
Primary FDA-qualified biomarker for PKU
Measured: 3 weeks
Fasting plasma LNAAs, dried blood spots (finger-prick method)
Secondary biomarkers such as the plasma Phe/Tyr ratio, Tyr/LNAA, Trp/LNAA ratio
Measured: 3 weeks
Urine peripheral biomarkers of neurotransmitters, dried urine spots
6-sufatoxymelatonin and dopamine
Measured: 3 weeks
Computerized neuropsychological testing (responses over study iPad from home)
Cambridge Neuropsychological Test Automated Assessment Battery (CANTAB) customized for study
Measured: 3 weeks
PKU-QOL Questionnaire Adult version (responses over study iPad from home)
65-item (20 min) Patient-Reported Outcome Measure of the impact of PKU and the PKU diet on quality of life
Measured: 3 weeks
Psychological General Well-Being Index (responses over study iPad from home)
22-item (15 min) Patient-Reported Outcome Measure of well-being
Measured: 3 weeks
Adult ADHD Self-Report Scale (ASRS v1.1)
9-item inattention subscale (10 min) Patient-Reported Outcome Measure of attention
Measured: 3 weeks
3-Day Diet Record
Complete recording of 24-hr intake for 3 days (45 min)
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2021
- Study start1 Sep 2023
- Primary completion31 Jul 2024 (estimated)
- Study completion31 Jul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PhenylketonuriasStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized controlled trials in individual patients (interventional N-of-1 RCTs) offer an alternative research design to parallel group randomized controlled trials. The N-of-1 study attempts to determine the more effective treatment for one patient using multiple crossovers, with repetition providing statistical power.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- National PKU Alliance
- Responsible party
- Principal investigator, Shoji Yano, LAC+USC Medical Center
- Investigators
- Shoji Yano, MD, PhD, Principal investigator, Keck School of Medicine at USC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05174559
- Sponsor's protocol ID
- LNAA for PKU
- Status last verified
- Nov 2023
- First submitted
- 13 Dec 2021
- Last updated
- 4 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Can Care of Adult PKU Be Improved With Additional Dietary Large Neutral Amino Acids: An N-of-1 Study
- ClinicalTrials.gov ID
- NCT05174559
- Acronym / sponsor ID
- LNAA for PKU
- Conditions
- Phenylketonurias
- Keywords
- N-of-1 randomized controlled trials
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Collaborators
- National PKU Alliance
- Study start
- 1 Sep 2023 (actual)
- Primary completion
- 31 Jul 2024 (estimated)
- Study completion
- 31 Jul 2024 (estimated)
- First posted
- 30 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research investigates the effects of combining a phenylalanine restricted diet (usual care) with LNAA supplementation (adjuvant LNAA) in well-controlled adults with classical PKU. The hypothesis is that symptoms are improved in well-controlled patients who receive adjuvant LNAA therapy compared with diet monotherapy. Six symptomatic classical PKU adults will be enrolled to test the hypothesis in a small series of N-of-1 randomized controlled trials over 18-weeks. All assessments will be collected in patient's homes. A 3-month follow-up period will assess the longer-term effects of adjuvant LNAA in patients who show clinical benefit at the end of the intervention period.
Detailed description
Clinical care of PKU confronts an increasing proportion of early-treated well-controlled adults, with a treatment goal that quality of life be as normal as possible. Even adults who have successfully managed their blood phenylalanine levels from birth can have symptoms which impact daily function. New therapies that target symptoms are needed, especially for symptomatic well-controlled classical adults with few treatment options. In Denmark and the LAC+USC U.S. clinic, adults are offered large neutral amino acid (LNAA) supplements when diet monotherapy becomes less effective for symptom management, or the patient wants a less restrictive diet. Many patients report improved symptoms. LNAA supplementation doesn't significantly reduce blood phenylalanine, suggesting a different mechanism for patient perceived benefits. Both LNAA supplementation and a phenylalanine restricted diet aim to improve brain neurotransmitter biochemistry to optimize outcomes through dietary intervention. The overall objective of this research is to evaluate additional dietary LNAAs on symptom management in adults with classical PKU at an individual level. N-of-1 randomized controlled trials will provide the highest level of evidence. The scientific premise is that manipulation of dietary LNAAs affects blood LNAA concentrations. LNAAs compete with phenylalanine for a shared transporter from blood to brain, dependent on blood concentrations and transporter affinities. Higher blood phenylalanine levels in adult PKU, with high transport affinity, produces excessive phenylalanine brain entry at the expense of other LNAAs. Insufficient LNAAs impairs synthesis of chemicals in the brain (neurotransmitters), a suggested mechanism of action for adult PKU symptoms. Additional dietary LNAAs may help to overcome this limitation of adult usual care. The study uses established PKU treatment products (medical foods) and biomarkers, (1) to determine effect of the adjuvant LNAA diet in symptom management; and (2) to evaluate correlations between changes in biomarkers and changes in symptoms during the intervention. Should findings show additive clinical value of LNAAs to the PKU diet, the strategy may become a useful adjunct. For participants, results will bring them closer to evidence-based individualized care. This work could advance the field closer toward personalized management.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized controlled trials in individual patients (interventional N-of-1 RCTs) offer an alternative research design to parallel group randomized controlled trials. The N-of-1 study attempts to determine the more effective treatment for one patient using multiple crossovers, with repetition providing statistical power.
| Arm | Type | Receives |
|---|---|---|
| Active LNAA | Active comparator | Other: PreKUnil® LNAA Medical Food for PKUActive LNAA tablets are given to each participant in 3 multiple crossovers for a total exposure to the Active Comparator 3 times. The allocation is randomized within each cycle of two treatments (active/inactive). There are 3 total cycles for each participant. The intervention is PreKUnil® tablets. |
| Inactive LNAA | Placebo comparator | Other: PreKUnil® LNAA Medical Food for PKUInactive LNAA tablets (placebos) are given to each participant in 3 multiple crossovers for a total exposure to the Inactive Comparator 3 times. The allocation is randomized within each cycle of two treatments (inactive/active). There are 3 total cycles for each participant. The placebo intervention is PreKUnil® placebo tablets. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- age ≥ 18 years
- diagnosis of classical PKU (blood phenylalanine ≥1200 µmol pre-treatment or off-treatment
- ≥ 2 PKU-related symptoms with clinically meaningful negative impact on daily life
- is in regular clinical monitoring and is treated with a PKU diet with a natural protein restriction and medical foods
- average blood phenylalanine levels between 360 and 900 µmol in past one year
Key exclusion criteria (4 listed)
- women who are breastfeeding, pregnant or planning to become pregnant in the next year
- use of adjuvant PKU treatments (LNAAs, Kuvan®, Palinziq®) within past 3 months
- use of psychotropic medications, melatonin, or any serotonin-reuptake inhibitors within past 3 months
- demonstrates insufficient motivation or time required to complete full trial
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PreKUnil® LNAA Medical Food for PKUPreKUnil® LNAA Medical Food for PKU is a commercially available active LNAA treatment product for PKU. PreKUnil® inactive LNAA is a customized placebo for this research. | Other | Active LNAA, Inactive LNAA |
Primary outcome
Personalized Symptom Index
Time frame: 3 weeks
Assesses the subjective effect of the interventions on the personally relevant two most bothersome symptoms for the individual patient as identified in a Symptom Elicitation Interview
8 secondary outcomes
Absolute plasma phenylalanine concentration, dried blood spots (finger-prick method)
Time frame: 3 weeks
Fasting plasma LNAAs, dried blood spots (finger-prick method)
Time frame: 3 weeks
Urine peripheral biomarkers of neurotransmitters, dried urine spots
Time frame: 3 weeks
Computerized neuropsychological testing (responses over study iPad from home)
Time frame: 3 weeks
PKU-QOL Questionnaire Adult version (responses over study iPad from home)
Time frame: 3 weeks
Psychological General Well-Being Index (responses over study iPad from home)
Time frame: 3 weeks
Adult ADHD Self-Report Scale (ASRS v1.1)
Time frame: 3 weeks
3-Day Diet Record
Time frame: 3 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shoji Yano, MD, PhD principal investigator
Keck School of Medicine at USC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PreKUnil® LNAA Medical Food for PKU in people with Phenylketonurias, run by University of Southern California at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Personalized Symptom Index (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2023.